Background: Sepsis is fatal presentation which affects many systems with possible progression to organ dysfunction and organ failure. Among these organs liver plays an important role in the prognosis of this syndrome. This study investigated the effects of hyperbaric oxygen (HBO) and normobaric oxygen (NBO) therapies on liver damage and oxidative stress in an experimental sepsis model. Materials and methods: Forty males Wistar rats were randomized into 4 groups as sham group (n=10), control (Sepsis+Cefepime) group (n=10), HBO (Sepsis+Cefepime+HBO) group (n=10), and NBO (Sepsis+Cefepime+NBO) group (n=10). Five days after sepsis induction, animals were sacrificed. The oxidative stress parameters, malondialdehyde (MDA) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) for antioxidant response were measured in liver tissue. Neutrophil migration using myeloperoxidase (MPO) activity and its contribution to liver damage was evaluated. Results: While MDA levels in HBO group were found to be lower than those in the control group, and comparable to those in the sham group, no difference was detected in the MDA levels between the control and NBO groups. SOD levels in NBO group were detected to be significantly higher than the control group. GSH-Px enzyme activity in HBO and NBO groups was at similar levels. Even though MPO levels in HBO group appeared to be lower than the control group, the difference did not reach statistical significance. When MPO levels and histopathological examination were evaluated, it was observed that neither HBO nor NBO administration in addition to antibiotherapy provided decrease in neutrophil infiltration which has an important role in liver damage. Conclusion: The benefit of HBO in the treatment of sepsis in addition to the use of antibiotics has also been confirmed to be successful in this study. Furthermore the data obtained from NBO applications in this study, is thought to be potentially useful for sepsis treatment.

Bu calismada, N-asetilsisteinin, kronik pankreatit hayvan modelinde fibrozis, atrofi ve oksidatif stres uzerindeki etkisini degerlendirmeyi amacladik. Kronik pankreatit, ratlarin ana pankreatik kanallarina 0.4 ml, %2’lik trinitrobenzen sulfanik asit (TNBS) enjeksiyonu ile uyarilir. 60 Sprague-Dawley sicani dort gruba randomize edildi; Grup I (n= 15): salin (sham), Grup II (n= 15): fibrozis + N-asetilsistein (NAC), Grup III (n= 15): fibrozis (TNBS), Grup IV: etanol. 8. haftanin sonunda tum ratlar sakrefiye edildi ve pankreatik dokular, oksidatif stres belirtecleri, fibrozis ve atrofi progresyonlari incelendi. NAC grubunda doku malondialdehid (MDA) duzeyleri anlamli olarak dusuk bulunurken (p <0.001); superoksit dismutaz (SOD) ve glutation peroksidaz (GSH-Px) aktiviteleri TNBS grubuna gore anlamli olarak yuksek bulundu (sirasiyla p <0.001 ve p <0.001). Dokulardaki histopatolojik incelemede NAC grubunun histopatolojik skorunun TNBS grubundan anlamli derecede dusuk oldugu izlenirken (p<0.003) oksidatif stres ile histopatolojik skordaki artis arasinda anlamli bir iliski oldugu saptandi (histopatolojik skor/MDA: p<0.03, SOD: p<0.04, GSH-Px: p<0.02). Sonuc olarak, NAC uygulamasi kronik pankreatitte oksidatif stresi azaltmakta olup fibrozis ve atrofi uzerinde yararli etkilere sahiptir.

ing & Indexing Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi’nde yayınlanan içerikler yazar(lar)a aittir. Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, dergi editörleri, çalışanları ve yayıncı bu yazılar için mali, hukuki ve diğer yönlerden sorumluluk kabul etmemektedir. Published content of Medical Journal of Mugla Sitki Kocman University is in authors’ own responsibility. Mugla Sitki Kocman University School of Medicine, editors, employees and the publisher do not accept any financial, legal or any other liability for the published material. Bu dergide yer alan yazı, makale, fotoğraf ve illüstrasyonların elektronik ortamlarda dahil olmak üzere kullanma ve çoğaltma hakları Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi’ne aittir. Yazılı ön izin olmaksızın materyallerin tamamının ya da bir bölümünün çoğaltılması yasaktır. Her hakkı saklıdır. Rights to the use and reproduction, including in the electronic media, of all communications, papers, photographs and illustrations appearing in this journal belong to the Turkish Journal of Physical medicine and Rehabilitation, Reproduction without prior written permission of part or all of and material is forbidden. All rights are reserved. İletişim / Correspondence Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi Kötekli Mahallesi Marmaris Yolu Bulvarı No:50 48000/Menteşe/MUĞLA/TURKEY Tel :+ 90 252 211 48 00 Faks / Fax :+90 252 211 13 45 e-posta / e-mail : muglatipdergisi@mu.edu.tr İnternet Adresi / URL: http://dergipark.gov.tr/muskutd Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi Medical Journal of Mugla Sitki Kocman University Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi Medical Journal of Mugla Sitki Kocman University Muğla Tıp Dergisi Mugla Medical Journal ISSN:2148-8118 e-ISSN: 2618-6020

PURPOSE Rapamycin reduces hepatic fibrosis by inhibiting hepatic stellate cell activation. The present study investigated whether rapamycin treatment could modify the degree of fibrosis, cellular apoptosis and oxidative stress (OS) in an experimental model of CP. METHODS Fifty-five male, Sprague-Dawley rats weighing 200-400g were randomized into four groups. CP was induced by intraductal trinitrobenzene sulfonic acid (TNBS) infusion in group A (n = 15) and group B (n = 15). Group C (n = 15) received intraductal TNBS and was killed for histologic confirmation at four weeks. Group D (n = 10) received intraductal saline instead of TNBS. Group A and group D received oral rapamycin (2 mg/kg/d) for two weeks after CP was induced while group B received oral tap water instead of rapamycin. Blood and pancreatic tissue specimens were collected and oxidative stress parameters, fibrosis and cellular apoptosis were determined. RESULTS Tissue and blood malondialdehyde (MDA) levels were significantly lower in rapamycin treated group compared to controls (p < 0.001). Superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities were also significantly higher in the active treatment group (p < 0.001 for both). Tissue and blood MDA, SOD, GSH-Px measurements was similar in rapamycin group and pancreatic cannulation group (p > 0.05). Histopathologic fibrosis scores were similar in rapamycin and control groups. Apoptotic cell counts tended to be lower in rapamycin treated animals. CONCLUSIONS Administration of rapamycin alleviated OS and, in part, prevented apoptotic cell death in experimental CP, but did not reduce fibrosis.

The innate immune network is responsible for coordinating the initial defense against potentially noxious stimuli. This complex system includes anatomical, physical and chemical barriers, effector cells and circulating molecules that direct component and system interactions. Besides the direct effects of breaching pulmonary protective barriers, cyclic stretch generated during mechanical ventilation (MV) has been implicated in the modulation of the innate immunity. Evidence from recent human trials suggests that controlling MV-forces may significantly impact outcome in acute respiratory distress syndrome. In this paper, we explore the pertinent evidence implicating biotrauma caused by cyclic MV and its effect on innate immune responses. Introduction The natural or innate immune system is present in some form in most living organisms and consists of mechanisms for defending the host against foreign invaders and for healing injured tissues. We now know that many of the mechanisms of resistance to infection are also involved in the individual’s response to noninfectious foreign substances and environmental stresses, including mechanical stretch. Furthermore, mechanisms that normally protect individuals and eliminate foreign substances are themselves capable of causing tissue injury and disease. This inherent defense network includes anatomical, physical and chemical barriers, circulating molecules, cells with specific phagocytic or lytic abilities, and soluble mediators that orchestrate the activities of each component and their interactions with the acquired immune system. Normally, this is a well integrated system of host defense and preservation of self-integrity, in which numerous cells and molecules function cooperatively. However, dysregulation of the fine balance between proinflammatory and anti-inflammatory stimuli may explain the pathophysiologic processes that underlie syndromes such as sepsis and acute lung injury (ALI) [1]. Although patients undergoing positive pressure mechanical ventilation may have impaired lung function, and possibly impaired systemic immune defenses by virtue of their underlying lung pathology, further dysregulation of natural defenses occurs in these patients. The presence of an endotracheal tube bypassing natural upper airway defenses, decrease or loss of coughing, paralysis of bronchial ciliae, alterations in surfactant and phagocyte and epithelial defensins – a critical first line antibacterial defense mechanism – all contribute to impairment in host defense [2–4]. Apart from the direct effects of breaching pulmonary protective barriers, cyclic stretch generated during mechanical ventilation has been implicated in the modulation of the innate immune system. In this short review we revisit some of the pertinent evidence exploring the relationship between biotrauma caused by cyclic mechanical ventilation and its effect on innate immune responses. This is not intended to be a comprehensive and structured review of the Review Bench-to-bedside review: Biotrauma and modulation of the innate immune response Claudia C dos Santos1, Haibo Zhang2, Mingyao Liu3 and Arthur S Slutsky4 1Clinical Associate and Post Doctoral Fellow, Departments of Medicine and Critical Care Medicine, St. Michael’s Hospital, and Inter-Departmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada 2Assistant Professor, Departments of Medicine and Critical Care Medicine, St. Michael’s Hospital, and Inter-Departmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada 3Professor, Departments of Medicine and Critical Care Medicine, St. Michael’s Hospital, and Inter-Departmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada 4Vice President of Research, Departments of Medicine and Critical Care Medicine, St. Michael’s Hospital, and Inter-Departmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada Corresponding author: Arthur S Slutsky, arthur.slutsky@utoronto.ca Published online: 5 January 2005 Critical Care 2005, 9:280-286 (DOI 10.1186/cc3022) This article is online at http://ccforum.com/content/9/3/280 © 2005 BioMed Central Ltd

Objectives: This study was designed to evaluate effects of hyperbaric oxygen (HBO) plus 3-aminobenzamide (3-AB) cotreatment on tissue oxidative stress parameters (TOSp), tissue histopathology scores (THSc), and bacterial translocations (Bact-Trans) in an experimental model of severe acute pancreatitis (AP).Methods: Seventy-five Sprague-Dawley rats were randomized into 5 groups. Group 1 received sham. Severe AP was induced by intraductal taurocholate infusion and then group 2 received saline, group 3 received 3-AB, group 4 received 3-AB plus HBO, and group 5 received HBO. 3-Aminobenzamide (10 mg/kg per day, once daily, intraperitoneal) and saline (1 mL/kg) were started right after the induction, whereas HBO (2,8 atm pressure, BID, 90 minutes each) was started at the sixth hour. The rats were euthanized at the 54th hour, and TOSp, THSc, and Bact-Trans were studied.Results: In treatment groups 3 and 5, Bact-Trans (P < 0.05, P < 0.05), TOSp (P < 0.05, P < 0.05), and THSc (P < 0.001, P < 0.001) were significantly lower than controls. In addition to these findings, group 4 (cotreatment) showed the most significant effect on Bact-Trans and THSc (P < 0.001, P < 0.001) and also better in TOSp (P < 0.02).Conclusions: Poly(ADP-ribose) polymerase inhibition by 3-AB and HBO treatment alone was effective in the course of severe AP, and favorable with cotreatment because of the improved cascades of inflammatory process by different aspects.

The application of stereologic techniques to the analysis of the nervous system has greatly contributed to the evaluation of the normal and pathological anatomy of the aging brain. Currently, the hippocampus still holds secrets about the aging process. Experimental researches on hippocampus morphology may contribute to the future researches. This study presents the volume and weight of left hippocampus using a stereological technique on light microscope. The mean weight of the encephalon without cerebellum was 6.1 ± 0.1 g. The mean weight and the volume of the hippocampus were (mean ± SD) 0.28 ± 0.02 g and 0.28 ± 0.02 cm3, respectively. The mean coefficient of error for the stereological volume estimation of the hippocampus was 0.03. The individual volume estimation of the subjects may be achieved by the Cavalieri method. Investigators believed that the findings and the applied technique in this study may be useful for clinicians.

Acetyl Cholinesterase inhibitors (AChEIs) are drugs commonly prescribed to treat cognitive and neuropsychiatric symptoms of AD. This treatment, based on the cholinergic hypothesis, enhances cholinergic function in the brain, but also acts in a complex manner on the cerebrovascular innervations. AChEIs may not only augment cerebral perfusion through their stimulant effects on the intrinsic cholinergic cerebrovascular innervations, but they may also promote vasoconstriction through blockade of nicotinic receptor mediated autonomic vasodilatation. Previously, however, it was demonstrated that there isn't any short-term effect of ChEIs on ortostatic hypotension in Alzheimer Disease, long-term effect of AChEIs on the ortostatic Hypotension in elderly patients with Alzheimer Disease has not evaluated. One hundred and eighty four elderly patients with AD who had undergone comprehensive geriatric assessment including cognitive and nutritional states, basic and instrumental daily living activity indexes were evaluated and preliminary results of 77 patients who completed 6-month AChEIs treatment were presented in the study. The patient's demographic characteristics, postural blood pressure changes, and laboratory values were evaluated. OH diagnosis was defined as a drop of at least 20 mm Hg in systolic BP (SBP) and/or 10 mm Hg in diastolic BP (DBP) upon the change in position. In here, the prevalence of OH in elderly patients with AD was found to be 35.1%. There were no significant differences in age, gender, and number of medications regularly used between the groups with OH and without OH (p > 0.05; Table). Both groups were analyzed in order to reveal a possible association between OH and hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and depression. However no significant differences were found among the groups (p> 0.05 for each comparison). At the end of the 6-month AChEIs treatment period, this prevalence of OH was found as 37.7% (p>0.05). However, s ubgroup analyses of these preliminary results of 77 patients were demonstrated that frequency of OH decreased in those treated with rivastigmine (from 45.2% to 35.5%) and increased in those treated with donepezil (from 29.4% to 44.1%). It was also demonstrated that this frequency in those treated with galantamine didn't change (25%). Although these results have been preliminary, it has been demonstrated striking results related to orthostatic hypotensive effects of rivastigmine and donepezil in elderly patients with AD. In addition, since OH is closely related with mortality and morbidity in elderly population, evaluation the changes in postural blood pressure should be routinely done in elderly patients with AD.

Purpose: Sirolimus reduces hepatic fibrosis by inhibiting hepatic stellat cells. We aimed to show the similar effect by inhibiting the pancreatic stellat cells in experimental chronic pancreatitis. Methods: In our study 55 male, Sprague-Dawley rats weighing between 200 and 400 grams randomized into four groups. Chronic pancreatitis is induced by injection of 0,4 ml, 2% trinitrobenzene sulfanic acid (TNBS) into major pancreatic duct. Group A (n=15): chronic pancreatitis + sirolimus; TNBS induction, 4 weeks later, 2 mg/kg/day oral sirolimus for 2 weeks; Group B (n=15): Chronic pancreatitis + placebo; TNBS induction, 4 weeks later 2 ml/kg/day oral water for 2 weeks. Group C (n=15): Chronic pancreatitis; TNBS induction, 4 weeks later sacrified. Group D (n=10): Pancreatic cannulation + sirolimus; 0,4 ml, % 0,9 NaCl injection into pancreatic duct, 4 weeks later 2 mg/kg/day oral sirolimus for 2 weeks. At the end of the ninth week in group of A, B and D all rats have been sacrifi ced, and rat pancreatic tissues, oxidative stress markers and progression of fibrosis and apoptsosis have been examined Results: Tissue and blood malondialdehyde (MDA) levels has been found significantly lower in sirolimus group compared to placebo group (p<0,001) and superoxide dismutase (SOD) and glutation peroxidase (GSH-Px) activities have been significantly higher. (Respectively p<0,001 and p<0,001). Tissue and blood MDA, SOD, GSH Px levels was no different significantly in the sirolimus group compared to the pancreatic cannulation group (p>0,05) (Table 1). Histopathological analysis of the tissues revealed that score of sirolimus group was significantly higher at respect to other groups (p<0,05). The levels of apoptotic cell of sirolimus group was higher at respect to placebo group, but this was not statistically significant (Table 2).Table: Table. Levels of oxidative stress markers in tissue and bloodTable: Table. Histopathological FindingsConclusion: Administration of sirolimus decreases oxidative stress in experimental chronic pancreatitis, but hasn't beneficial effects on fibrosis and apoptosis.

Elderly people have an increased risk of falls, which may lead to disabling injury and death, with 30% of them falling one or more times each year, and falls are one of the most important problems for elderly patients with severe Alzheimer Disease. However, recent studies and our experience have demonstrated that gait and balance impairments can develop in elderly people with early stages of Alzheimer's Disease. In addition, no studies to date have evaluated effects of cholinesterase inhibitors on gait and balance impairments in these patients. Therefore, this study designed to examine the effects of cholinesterase inhibitors on gait and balance impairments in elderly patients with Alzheimer's Disease. Of 128 consecutive elderly patients who were newly diagnosed with AD, 90 were enrolled and underwent comprehensive geriatric assessments including MMSE, MoCA, ADL, Tinetti Performance Oriented Mobility Assessment (Gait and Balance) (POMA). 68 consecutive elderly patients Alzheimer Disease treated with a flexible 4-weekly cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) dose titration regimen up to maximum tolerated dose. All of the patients also underwent comprehensive geriatric assessments at the 24 weeks after initiation of treatment with cholinesterase inhibitors. There were no significant changes relative to the baseline in any of the gait and balance scores at the 6-month treatment with cholinesterase inhibitors (p>0.05). In addition, any of cholinesterase inhibitors was not superior to each other (for each comparison p>0.05). It was demonstrated that cholinesterase inhibitors were not improve gait and balance scores in elderly patients with Alzheimer's Disease.

BACKGROUND & OBJECTIVES:Translocation of bacteria from the gut is an important factor in the development of septic complications and mortality in acute pancreatitis (AP). The present study was designed to assess the effects of infliximab treatment on bacterial translocation (BT) in experimental acute necrotizing pancreatitis.METHODS:Male Sprague-Dawley rats (n=45) were allocated into three groups. AP was induced in group II (positive control, n=15) and group III (Infliximab; n=15) by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (Sham; n=15) received normal saline infusion into the common biliopancreatic duct as placebo. Groups I and II were treated by normal saline and group III was treated with infliximab intraperitoneally on 6, 30 and 54 h after induction of pancreatitis. All surviving animals were killed 60 h after the induction of pancreatitis, and specimens were collected for amylase measurement as well as histopathologic and microbiologic examinations.RESULTS:Oedema, acinar cell necrosis, inflammatory infiltration, haemorrhage, fat necrosis and perivascular inflammation in group III rats were decreased with infliximab treatment when compared with group II (P<0.001). BT to mesentery lymph node in groups I, II and III were 20, 100 and 46 per cent, respectively. BT to peritoneum and pancreas in group III was lower than group II (P<0.05).INTERPRETATION & CONCLUSIONS:Infliximab administration resulted in beneficial effects on BT and histopathologic changes in the experimental necrotizing pancreatitis. Whether anti-TNF therapy has a role in prevention of complications of ANP needs to be established.

Cholinesterase inhibitors (ChEIs) are currently considered to be the first line treatment for Alzheimer's disease (AD). Although the target organ for cholinesterase inhibitors is the brain, they may adversely affect cardiac function, and their cholinergic side effects on the cardiovascular system are still unclear. In this study, it was aimed to examine the side effects caused by donepezil, rivastigmine and galantamine on cardiac rhythm pulse pressure changes in in elderly patients with AD. 190 consecutive elderly patients with AD were enrolled the study. Elderly patients with AD divided into three groups according to ChEIs including donepezil, rivastigmine and galantamine. The ECG parameters and pulse pressure were recorded at the baseline and 1 month after dose of 10 mg/d of donepezil, 10 cm2/d of rivastigmine and 24 mg/d of galantamine. 154 of 190 consecutive elderly patients completed the study. There were no significant changes relative to the baseline in any of the ECG parameters or pulse blood pressure with any of the administered ChEIs (p>0.005 for each comparison) (Figure 1 and 2).

As the world population has aged, the number of people affected by Alzheimer Disease is rapidly increasing in the world. It is important for clinicians to recognize early signs and symptoms of dementia and to note potentially modifiable risk factors and early disease markers. Accumulation of A┚ peptides may be the key event in pathogenesis of AD. The exact mechanism by which A┚ peptide deposition induces neurotoxicity is unclear, but it appears the oxidative stress plays an important role. Oxidative stress is extensive in AD and A┚ peptides stimulate oxidative stress by both direct and indirect mechanisms. A┚ peptides by themselves may act as enzymes and can bind to mitochondrial proteins resulting in the generation of free radicals. Furthermore, A┚ peptides generate oxidative stress via neuroinflammation. Considerable evidence has supported that neuroinflammation is associated with AD pathology. In addition, in AD, vascular injury and parenchymal inflammation perpetuate the cycle of protein aggregation and oxidation in the brain, and diffuse pathological changes include cerebral amyloid angiopathy, affecting more than 90% of patients with Alzheimer’s disease, capillary abnormalities, disruption of the blood-brain barrier, and large-vessel. In addition, it was reported that clearance of A┚ along diseased perivascular channels and through the blood-brain barrier is impeded in AD atheroma and that deregulation of A┚ transport across the capillary blood–brain barrier is caused by the imbalanced expression of low-density lipoprotein receptor-related proteins and receptors for advanced glycation end products. Besides, insulin resistance and hyperinsulinemia are implicated in a number of pathophysiological processes related to AD. It was demonstrated that reduced brain insulin signaling is associated with increased tau phosphorylation and A┚ levels in a streptozotocin induced model of diabetes mellitus. Moreover, insulin promotes the release of intracellular A┚ in neuronal cultures and accelerates A┚ trafficking to the plasma membrane. In addition, impaired insulin or insulin like growth factor-1 (IGF-1) signaling can result in the hyper-phosphorylation of tau, which can cause cell death mediated by apoptosis, mitochondrial dysfunction or necrosis and promote oxidative stress, which contributes to the neurodegeneration cascade and leads to dementia-associated behavioral and cognitive deficits.

Objective: Antibiotics are widely used in the treatment of infections and for empirical treatment purposes. Despite this common consumption of antibiotics, it is difficult to state that antibiotics are chosen and used consciously. This study was planned to determine the prevalence of prescribing antibiotics in Turkey.Methodology: This cross-sectional study was conducted in November 2003. The study was carried out in a total of 46 primary care health centers of the following cities; Central Anatolian, Western Anatolian, Eastern Anatolian regions.Results: Two hundred sixty seven physicians participated in the study, 38.9% (104) of which were women and 61.1% (163) were men. The proportion of antibiotic prescription was by 22,6%, and the most frequently chosen antibiotics were 15.6% (3301) Amoxycilline+Clavulanic acid (Amox/Clav), 15.1% (3184) Ampicilline+Sulbactam 12.84% (2711), respectively. When prescriptions with antibiotics were evaluated according to diagnosis, the most frequent diagnoses were found to be as follows: 53.3% (11430) Acute Upper Respiratory Infections, 16.4% (3516) Urinary Tract Infections.Conclusions: The findings of the study suggest that primary healthcare physicians most often prescribe for acute respiratory tract infections, and prescribe Amoxycilline+Clavunic the most. It may be argued that more extensive studies are needed in this field.

Increased serum insulin levels and reduced peripheral insulin activities seen in insulin resistance syndrome are associated with age-dependent cognitive impairment and Sporadic Alzheimer's Disease (SAD), suggesting a disturbance in the insulin signalling system in the brain and possibly being one of the causes of dementia. Therefore, the streptozotocin (STZ)-induced animal may be an appropriate model for the investigation of SAD and related dementia. This study was designed to investigate the beneficial effect of Curcumin (CUR), a neuroprotective agent, on intracerebroventricular (ICV) STZ-induced cognitive impairment in rats. For this purpose, adult male Wistar rats were bilaterally ICV injected with STZ (3 mg/kg). An artificial cerebrospinal fluid (aCSF) was given to the control group (SHAM) instead of STZ on days 1 and 3. Learning and memory performance were assessed using the "passive avoidance task" and the "Morris water maze test". After confirmation of acquisition impairment with these tests, the STZ group was divided into two subgroups: STZ + vehicle (Vh) and STZ + CUR. The rats in the SHAM and STZ + Vh groups were administered intraperitoneally with 0.5 ml Vh and the rats in the STZ + CUR group were treated intraperitoneally with CUR (300 mg kg(-1) day(-1) in Vh) for 10 days starting from the 25th day after STZ injection. The Morris water maze test was reapplied on the 35th day after STZ injection and all of the rats were sacrificed on day 36 for quantitation of IGF-1 and for histopathological evaluation. Rats in the STZ + CUR group were found to have a higher performance in cognitive tests than rats in the STZ + Vh group (P < 0.01). In parallel with the cognitive tests, IGF-1 levels were decreased in all of the STZ-injected groups (1.78 +/- 0.34) compared to the SHAM group (3.46 +/- 0.41). In contrast, CUR treatment significantly increased IGF-1 levels (P < 0.001). The degree of neuronal loss decreased after CUR treatment compared to the SHAM group (P < 0.02). These results clearly indicate that CUR treatment is effective in reducing the cognitive impairment caused by STZ in rats, and may be a potential therapeutic agent for altering neurodegeneration in SAD.