Prevention of biochemical changes in gamma-irradiated rats by some metal complexes.

The formation of superoxide partially accounts for the well-known oxygen enhancement of radiation-induced biochemical changes and cell damage. Radioprotective effects of copper (II), manganese (IV) or vanadium (IV) complexes, of superoxide dismutase-mimetic activity, on body weight, survival rate and some biochemical parameters in pre-treated irradiated, untreated irradiated and treated non-irradiated female albino rats have been studied 24 h after whole body gamma-irradiation at a dose level of 6 Gy. Survival time, body weight, red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin (Hb) concentration, percentage of hematocrit (Hct%), reduced glutathione (GSH), serum total protein, albumin, globulin (G), blood urea, creatinine and cholesterol were estimated, as well as the activities of blood superoxide dismutase (SOD), glutamate-oxaloacetic (GOT) and glutamate-pyruvic (GPT) transaminases, and alkaline phosphatase were assessed. A significant decline was shown in body weight, survival rate, the mean values of RBC and WBC counts, Hb and Hct percentages, and GSH concentration, as well as blood SOD activity, in whole body gamma-irradiated rats compared with the control non-irradiated rat group. The mean activity values of alkaline phosphatase, GOT and GPT, as well as the average values of blood urea, creatinine, total cholesterol, total protein and globulin were significantly elevated, while the average values of albumin and the albumin/globulin ratio were decreased in gamma-irradiated rats compared with the corresponding values of the normal control rat group. Pretreatment of rats with either manganese or vanadium complexes resulted in a significant increase in survival rate and body weight over that of the non-treated irradiated rat group. Pretreatment of rats with copper (II), manganese (IV) or vanadium (IV) complexes caused a significant increase in RBC and WBC counts, Hb concentration, HCt (%), GSH content and SOD activity in blood when compared to the irradiated rat group without treatment. The administration of copper (II), manganese (IV) or vanadium (IV) complexes prior to irradiation exposure resulted in a significant decrease in GOT and GPT activities in addition to blood urea, creatinine, cholesterol, globulin and total protein contents, while each complex exhibited a significant increase in plasma alkaline phosphatase, albumin, and the albumin/globulin ratio compared to the untreated irradiated rat group. Administration of vanadium (IV), manganese (IV) or copper (II) complexes in non-irradiated rats caused a significant increase in SOD activity without changing other biochemical parameters compared with the corresponding values of the normal control rat group. We conclude that these metallo-elements, particularly manganese (IV) and vanadium (IV) complexes of 2-methylaminopyridine, have radiation protection and radiation recovery. Furthermore, these metal complexes offer a new approach to overcome the pathological effects of ionizing radiation and suggest their use as a physiological approach to preventing or perhaps predominantly facilitating recovery from radiation injury.     

Ichthyosis associated with widespread tinea corporis: report of three cases

Ichthyoses are a common group of keratinization disorders. A non-inflammatory generalized persistent skin desquamation is observed. It is characterized by increased cell turnover, thickening of the stratum corneum and functional changes of sebaceous and sweat glands. All of these favor fungal proliferation. Dermatophytes may infect skin, hair and nails causing ringworm or tinea. They have the ability to obtain nutrients from keratinized material. One of its most prevalent genera is Trichophyton rubrum. Although tineas and ichthyoses are quite common, the association of the two entities is rarely reported in the literature. Three cases of ichthyosis associated with widespread infection by T. rubrum are presented. Resistance to several antifungal treatments was responsible for worsening of ichthyosis signs and symptoms.     

Successful single-word writing treatment: Experimental analyses of four cases

Background: Individuals with severe aphasia may fail to regain spoken language, so that treatment should target other communication modalities such as writing. There is relatively limited documentation of successful writing treatment, particularly in individuals with severe aphasia. Aims: The present study was designed to examine treatment outcomes in response to two writing treatment protocols intended to rebuild single-word vocabulary for written communication. Methods & Procedures: Writing treatments were implemented with four individuals who had significant aphasia and severe agraphia. Two participants received Anagram and Copy Treatment (ACT) which involved arrangement of component letters and repeated copying of target words, along with a homework programme called Copy and Recall Treatment (CART) that included copying and recall of target words. The other two participants received the homework-based CART only. Single-subject multiple-baseline designs were used with sets of words sequentially targeted for treatment. Outcomes & Results: All four participants responded positively to treatment. Three of the participants had severely limited spoken language, so that mastery of written words provided a much-needed means of communication. The fourth participant, who had adequate spoken language for face-to-face conversation, employed his improved spelling for written messages such as e-mail. Conclusions: Single-word writing abilities may improve with treatment despite long times post onset and persistent impairments to spoken language.     

Subependymal nodules and giant cell tumours in tuberous sclerosis complex patients: prevalence on MRI in relation to gene mutation

Purpose

The purpose of this study was to estimate the association among the presence of subependymal nodules (SENs), subependymal giant cell tumours (SGCTs) and gene mutation in tuberous sclerosis complex (TSC) patients.

Methods

Clinical records and images of 81 TSC patients were retrospectively reviewed by two neuroradiologists in consensus. All patients were assessed for gene mutations and were categorized as TSC1 or TSC2 mutation carriers, or no-mutations-identified (NMI) patients. They underwent a brain magnetic resonance imaging (MRI) using 0.1 mmol/kg of gadobutrol. Any enhancing SEN?≥?1 cm and placed near the foramen of Monro was considered SGCT. Two MRI follow-up exams for each patient with SGCT were evaluated to assess tumour growth using Wilcoxon and chi-squared tests.

Results

Of 81 patients, 44 (54 %) were TSC2 mutation carriers, 20 (25 %) TSC1 and 17 (21 %) NMI. Nine (11 %) had a unilateral and three (4 %) a bilateral SGCT. Fifty of 81 patients (62 %) showed at least one SEN. None of the 31 patients without SEN showed SGCTs, whilst 12 (24 %) of the 50 patients with at least one SEN showed SGCTs (p?=?0.003). The association between the presence of SGCT or SEN and gene mutation was not significant (p?=?0.251 and p?=?0.187, respectively). At follow-up, the median SGCT diameter increased from 14 to 15 mm (p?=?0.017), whilst the median SGCT volume increased from 589 to 791 mm³ (p?=?0.006).

Conclusions

TSC patients with SENs are more likely to present with SGCT than those without SENs, in particular for TSC2 mutation carriers. The SGCT growth rate may be missed if based on the diameter instead of on the volume.     

Does type 2 diabetes mellitus promote intervertebral disc degeneration?

Purpose

LDD is an important cause of low back pain. Many people believe there is an adverse influence of type 2 diabetes (T2D) on lumbar intervertebral disc degeneration (LDD). We examined a population sample for epidemiological evidence of association.

Methods

Twin volunteers from the TwinsUK cohort having spine magnetic resonance (MR) scans coded for LDD and information about T2D were investigated in two ways. First, as a population sample and second as a cotwin case control study in twin pairs discordant for T2D. Other risk factors for LDD considered were age, body-mass index (BMI), smoking, and alcohol.

Results

In 956 twin volunteers T2D had a prevalence of 6.6 %. LDD score was higher in T2D twins (14.9 vs 13.1 p = 0.04) but was not an independent risk factor if the influence of age and BMI were included in the model. Discordant twin analysis (n = 33 pairs) showed no significant difference in LDD between twins having T2D and their unaffected cotwins.

Conclusions

Twins having T2D did manifest higher LDD scores but the effect was abrogated once BMI was included in multivariable analysis, showing it is not an independent risk factor for LDD. The population study had 80 % power at 0.1 significance level to detect a difference of 1.8 in LDD score (range of 0–60), so if there is an effect of T2D on LDD, it is likely to be small.

     

TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline

Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.

Three-reactive centered reagent (TCCA) mediated construction of spirooxindoles through an oxidative rearrangement of various N-protected tetrahydro-β-carbolines and total synthesis of natural alkaloids (±)-coerulescine and (±)-horsfiline.     

Amelioration of radiation-induced oxidative stress and biochemical alteration by SOD model compounds in pre-treated gamma-irradiated rats

INTRODUCTION: The role of metalloelements in tissue maintenance, function and response to injury offer a new approach to decreasing and/or treating radiation injury. We investigated the roles of CuL(2)SO(4), [MnL(2)O](2)Cl(4)(H(2)O)(2) and [(VL(2)O)(VL(2)H(2)O)]Cl(6) complexes (L=2-methylaminopyridine) of SOD-mimetic activities, in ameliorating the radiation-induced oxidative stress and alterations in some biochemical parameters in liver, kidney, spleen and brain in pretreated female rats exposed to gamma-irradiation. METHODS: Both untreated-rats and rats treated with the above complexes were subjected to whole-body gamma-irradiation (6 Gy). 5'-Nucleotidase (5'-NT), acetylcholinesterase (AChE), adenosne triphosphatase (ATPase), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSSG-R) were assessed as well as liver DNA and RNA contents and total protein concentration were estimated in tissue homogenates of the above organs. The same parameters were assessed in non-irradiated treated rats and normal control rats. Results were compared to irradiated non-treated and normal control rats. RESULTS: Pretreatment of gamma-irradiated rats with Mn(IV) or V(IV) complex produced a significant decrease in liver 5'-NT activity compared to the corresponding value of the untreated irradiated rats. In contrast, liver DNA and RNA contents and brain AChE and ATPase activities were significantly increased in irradiated rat group pre-treated with these metal complexes. Cu II, Mn IV or V IV complex inoculation prior to irradiation of normal rats exhibited a significant increase in SOD, CAT, GSSG-R activities and protein content of liver, kidney, spleen and brain homogenates compared with that of the untreated irradiated rats. The treatment of non-irradiated rats with these complexes produced a highly significant increase in mean activities of SOD and CAT, with no changes in other parameters vs. controls. CONCLUSIONS: Cu(II), Mn(IV) and V(IV) 2-methylaminopyridine complexes offer a physiological approach to ameliorate the radiation-induced biochemical alterations. In addition, they provide sufficient protection against radiation injury of radiosensitive tissues.     

Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats

Stem cell therapy has been considered a promise for damaged myocardial tissue. We have previously shown that S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increases the expression of several muscular markers and VEGF in mesenchymal stem cells, indicating that transplantation of SNAP-treated cells could provide better functional outcomes. Here, we transplanted SNAP-treated adipose tissue-derived stem cells (ADSCs) in rat infarcted myocardium. After 30 days, we observed a significant improvement of the ejection fraction in rats that received SNAP-treated ADSCs, compared with those that received untreated cells (p = 0.008). Immunohistochemical reactions showed an increased expression of troponin T–C and von Willebrand factor, and organized vascular units in the infarcted area of tissue transplanted with treated ADSCs. SNAP exposure induced intracellular S-nitrosation, a decreased GSH/GSSG ratio, but did not increase cGMP levels. Collectively, these results indicate that SNAP alters the redox environment of ADSCs, possibly associated with a pre-differentiation state, which may improve cardiac function after transplantation.