Insulin resistance and cognitive impairment in type II diabetes mellitus

Background: Type II Diabetes mellitus [DM] is a metabolic disorder that is characterized by high blood glucose because of the insulin resistance. Significant 1 more interest has been dedicated to the effect of type II diabetes on the brain. Along with cerebrovascular disease, type II diabetes is implicated in the development of other neurological co-morbidities

Aim of the work: To study cognitive functions in type II DM and the effect of insulin resistance on it

Subjects and methods: In the present study, cognitive function tests were done for 37 subjects; control [n= 17], type II DM [n= 20]. These tests include mini mental state examination [MMSE], Wechsler adult intelligence scale [WAIS], Wechsler memory scale [WMS] and Cognitive Event related potential [P300]. Circulating levels of glycosylated haemoglobin [HbA[1c]] and insulin were determined in venous blood samples of both groups

Results: MMSE was significantly lower in type II DM than control group [p-value = 0.034]. However no significant difference between type II DM and control group in WAIS and WMS except in visual reproduction [p-value = 0.048]. P300 latency was significantly longer in type II DM than controls [p- value 0.0001]. P300 amplitude was decreased significantly in type II DM than controls [p-value= 0.0001]. HbA[1c] and insulin was significantly higher in type II DM than controls [p-value= 0.0001]

Conclusion: type II DM is associated with cognitive impairment which may be due to insulin resistance

Evaluation of potential protective effects of curcumin versus metformin in experimentally-induced metabolic syndrome in rats

Metabolic syndrome [MetSyn] is the clustering of various interrelated risk factors of metabolic origin that increased incidence of cardiovascular diseases and type 2 diabetes. In this study the effectiveness of curcumin was evaluated in comparison with metformin in fructose-induced MetSyn disease in rats. Fructose was fed [10% solution in drinking water] for 8 weeks during which groups of rats were administered once daily vehicle [2% carboxy methyl cellulose], curcumin [40 and 80 mg/kg], metformin [100 and 200 mg/kg], their combinations and compared with group received tap water instead of fructose. The results revealed that induction of MetSyn was associated with glucose intolerance, insulin resistance alongside with increased weights of body and visceral fats. This was accompanied with an elevation of arterial blood pressure. Meanwhile, it caused disturbances in lipid profile [triglyceride, total cholesterol, HDL-C and LDL-C] and both oxidative stress [inalondialdehyde, 8-Iso-PGF[2alpha] and superoxide dismutase] and inflaminatory status [tumor necrosis factor-a, interleukin-6, C- reactive protein and adiponectin] parameters. Each of curcumin and metformin significantly prevents, to variable extents, the progression of most of these signs of MetSyn. Furthermore, the efficacy of each of the two drugs in question was significantly augmented upon their concurrent administration. These protective effects of the two drugs under investigation presumably may be relevant to their ability to reduce the oxidative stress and to ameliorate the inflammatory processes

Evaluation of potential curative effects of curcumin versus metformin in experimentally-induced metabolic syndrome in rats

Metabolic syndrome [MetSyn] is an important public health concern that predisposes individuals to the development of cardiovascular diseases and/or type 2 diabetes [T2D]. In the present study the curative effect of curcumin, the active ingredient of spice turmeric, was assessed in comparison with metformin, the antidiabetic agent, against fructose-fed rats [FFR] model of MetSyn. Seven groups of rats were fed with 10% fructose solution in drinking water for 8 weeks. At the beginning of 9[th] week, the groups of rats received respectively once daily the vehicle [2% carboxy methyl cellulose, CMC], curcumin [40 and 80 mg/kg], metformin [100 and 200 mg/kg] and their combinations for additional 2 weeks. Moreover, another group received plain tap water instead of fructose [normal control group]. The results of this study demonstrated that fructose-feeding was coupled with insulin resistance [IR], impaired glucose tolerance [IGT] together with elevation in body and visceral fat weights. This was associated with elevation of arterial blood pressure [ABP]. Meanwhile, fructose-feeding produced alterations in lipid profile [triglyceride [TG], total cholesterol [TC], High-density lipoprotein-cholesterol [HDL-C] and low-density lipoprotein-cholesterol [LDL-C]] and both oxidative stress [malondialdehyde [MDA], 8-iso-prostaglandin F[2 alpha] [8-iso-PGF[2 alpha]] and superoxide dismutase [SOD]] and inflammatory status [tumor necrosis factor-alpha [TNF-alpha] interleukin- 6 [IL-6], C-reactive protein [CRP] and adiponectin] parameters. Administration of curcumin and metformin significantly ameliorated, to variable extents, the development of most signs of MetSyn. Furthermore, the effectiveness of the two drugs was augmented upon their coadministration. These curative effects of curcumin and metformin may probably be relevant to their antioxidant and anti-inflammatory activities

Pharmacological and toxicological evaluation of the locally abused glue "Kolla" in rats

This work was devoted to study the physicochemical properties as well as the neuropharmacological and toxicological effects of the local glue "Kolla" which is commonly and widely abused by street children in Egypt. Chemical analysis showed that the main volatile solvent ingredient of "Kolla" is toluene and, thus, it was used as a reference toxic solvent in this study. Three different concentrations of each inhalant, glue and toluene, were investigated. Single inhalation [30 min] of both "Kolla" [1000, 4000 ppm] and toluene [5610, 22576 ppm] potentiated the sleeping time of pentobarbital. In their higher concentrations, "Kolla" [8000 ppm] and toluene [45153 ppm] antagonized the hypnotic action of pentobarbital. Single inhalation [30 min] of the tested substances produced motor incoordination and decreased locomotor activity of rats. The higher concentration of toluene [45153 ppm] increased this activity. Repeated daily inhalation [30 min/day for 10 days] of "Kolla" and toluene in the 3 tested concentrations increased locomotor activity of rats. Levels of Malondialdehyde [MDA.] in cortex and cerebellum increased after repeated inhalation of glue and toluene. Also, glutamate level in hippocampus increased after repeated inhalation of the two toxic inhalants. Extraction of liver, kidney and heart after 10 days of daily repeated inhalation showed some histopathological changes

Importance of inflammatory cytokines and endothelial peptides in predicting hypertensive left ventricular hypertrophy

Although it has been hypothesized that hypertension in part is an inflammatory disorder, the link between inflammation and endothelial disorders with hypertensive complications as left ventricle hypertrophy [LVH] is still marginal. This study was designed to investigate the role of inflammatory markers as interleukin-6 [IL-6], high sensitivity C reactive protein [Hs-CRP], endothelial peptides as endothelin-1 [EDN -1] and nitric oxide [NO] as well as serum lipid profile in predicting LVH. It also focused on the pathophysiological responsibility of inflammation and endothelial dysfunction in developing hypertensive LYH. To examine these hypotheses forty hypertensive patients were enrolled and divided by using echocardiography into hypertensive patients with normal left ventricular mass [Group I] and hypertensive patients with LVH [Group II]. Ten normotensive subjects were also included and considered as control group [C]. ELISA technique was used for measuring plasma concentrations of IL-6, Hs-CRP, EDN-1 by special kits, while serum NO and lipid profile were measured by spectrophotometer. Both hypertensive groups were relatively matched with each other regarding age, gender, body surface area and body mass index [BMI], however they were significantly greater than control. Serum levels of IL-6, Hs-CRP and END-1, were significantly higher and those of NO were significantly lower in both hypertensive groups compared to normotensives. Moreover, these changes were more obvious in hypertensive patients with LVK Additionally, estimation of serum lipid profile showed that levels of total cholesterol triglycerides, and low density lipoproteins [LDL-C] were significantly elevated and that of high density lipoproteins [HDL-C] were significantly reduced in group [II] compared to other groups. Among both hypertensive patients, LY mass index was significantly positively correlated with serum levels of IL-6, Hs-CRP, EDN-1, cholesterol, triglyceride, LDL-C and significantly negatively correlated with HDL-C hut not with age and NO levels. However, the slope of these relations was steeper in the hypertensive group with LVH. Besides, levels of IL-6 and EDN-1 were the most predictors [r= 0.849, P<0.0001, r= 0.889, P<0.0001 respectively] for LYH. The inflammatory markers are significantly increased in hypertensive patients with LVH. Increased EDN-l and lowered NO are also concerned to a greater extent in hypertensive LYH and this confirms a key pathophysiological role of inflammation and endothelium dysfunction in developing and progression of hypertension and LVH which is vital for recommending prophylactic and therapeutic strategies

study of anticonvulsant effect of some steroids on induced seizures in adult male mice

Hormones influence brain functions throughout life and might alter seizures susceptibility by affecting neuronal excitability. Alterations in gamma amino butyric acid [GABA,] ergic neurotransmission are associated with seizures disorders and consequently much of antiepileptic therapy is directed towards the GABA A receptor complex. In humans, seizures patterns are affected by some factors such as the onset of puberty, pregnancy and stress suggesting that there is an underlying hormonal component. the present study was conducted to evaluate the anticonvulsant effect and the possible mechanism of action of some steroid hormones. Progesterone, deoxycorticosterone [DOC] and dehydroepiandrosterone [DHEA] in experimentally induced seizures in male mice. This study was carried out on adult albino male mice weighing 24-26gm and included two experiments: experiment I, in which two models of seizures were used; pentylenetetrazol [PTZ] model and maximal electro-convulsive shock seizures [MES] model. In each model, the animals were divided into 5 groups. The first group was kept as a control group and each of the other 4 groups was subdivided into 3 subgroups, 20 animal each. The treated groups included: diazepam, progesterone, DOC and DHEA treated groups at different doses. In PTZ model, PTZ was given in a dose of 70 mg/kg by intraperifoneal [i.p.] injection to induce chemoconvulsant seizures while in MES model, the animal received a stimulus train of electric current 25 mA, 50 Hz through the brain via ear electric clip. Diazepam and hormones were given 30 mm prior to PTZ injection or MES induced seizures. Experiment II in which bicuculline, a GABA A receptor antagonist was used in a dose of 1 mg/kg subcutaneously [s.c] 15 mm prior to administration of hormones. The ictal activity [latency, duration of myoclonic seizures and percent of protection against seizures and mortality] was recorded in either experiment. It was observed that progesterone suppressed PTZ induced seizures where it significantly [P<0. 001] prolonged the latency and shortened the duration of myoclonic seizures as compared to control with median effective dose [ED 50] of about 20 mg/kg s.c. The protection against seizures was 60, 70 and 75% and against mortality was 100%. Also, DOC administration exhibited a potent significant anticonvulsant activity in PTZ model in comparison to control and nearly equal to diazepam treatment. The ED 50 of DOC was 5 mg/kg and complete protection against seizures and mortality was observed at 20 and 80 mg/kg. In MES model, administration of progesterone at.20 and 80 mg/kg induced no significant anticonvulsant effect and ED 50 war observed at a higher dose [160 mg/kg]. Treatment with DOC 5 mg/kg produced no anticonvulsant activity, ED 50 was 20 mg/kg and complete protection against seizures was reached at 80 mg/kg. Both in PTZ and MES model, diazepam at the all tested doses induced a significant anhiconvulsant effect, while DHEA lacked any anticonvulsant activity, even it has a convulsant effect. Pretreatment with. bicuculline prior to progesterone and DOC administration caused a significant reversal of the anticonvulsant activity of these hormones. These findings indicate that the steroid hormones; progesterone and DOC have a broad spectrum anticonvulsant activity in animal seizures models [especially PTZ model] mediated by GABA A receptor modulation. Therefore, they might be involved in the modification of seizures frequency and epilepsy and might have a clinical importance in the future treatment of seizures disorders in conjunction with the usual antiepileptic drugs. On the other hand, DHEA has no anti convulsant effect

Disturbance of some coagulation and fibrinolytic factors in essential hypertension

Hypertension is an established risk factor for acute coronary events. Growing evidence is now apparent that hypertension is accompanied by hypercoagulable and/or hypofibrinoltic state, both of which can be the cause of several cardiovascular risk factors noticed with hypertension. To show the relationship between hypertension and some components of fibrinolytic and coaguIation systems . In this study, the plasma levels of fibrinogen, FVII, D-dimer, t-PA and PAI-I were studied in three groups of male persons. A hypertensive group of patients [16], complicated hypertensive group [16] and a group of normotensive persons [16] were included in this work Patients were selected from outpatient clinic of Cardiology Department, Assiut University Hospital, during the period from December 2001 until December 2002. The mean plasma levels of fibrinogen, FFVII, t-PA, PAZ-I and D dimer before treatment of the hypertensive and complicated hypertensive groups were significantly higher than that of the normotensive group .The mean plasma levels of these factors [except FVII] in the complicated hypertensive group were significantly higher than that of the hypertensive group. After treatment of these groups, the mean plasma levels of all factors decreased significant and there was no significant difference between the two groups. It is clear from this study that there are disturbances in the levels of coagulation and fibrinolytic factors in hypertensive patients particularly in the complicated hypertensive patients. This indicates severity of disturbance of these factors in hypertensive patients making them risk factors for the development of coronary heart disease, myocardial infarction, unstable angina, etc