Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces infarction volume and neurological deficits in an embolic model of stroke

1. Stroke is accompanied by a robust inflammatory response, glutamate-mediated excitotoxicity, release of reactive oxygen species and apoptosis. Thiazolidinediones, which target the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-g, have been reported recently to exhibit potent anti-inflammatory and anti-oxidant actions and inhibit both neural excitotoxicity and apoptosis. 2. The present study was conducted to determine whether rosiglitazone, a potent thiazolidinedione for PPAR-g, would show efficacy against the cerebral infarction and neurological dysfunctions induced by embolic middle cerebral artery (MCA) occlusion in the rat. 3. Focal ischaemic injury was induced by embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3 or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after embolization. Forty-eight hours after MCA occlusion, brains were removed, sectioned and stained with a 2% solution of 2,3,5-triphenyltetrazolum chloride and analysed using a commercial image-processing software program. 4. When rosiglitazone was administered 1 h before embolization, it significantly reduced infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg, respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P < 0.001). Rosiglitazone-treated rats also demonstrated improved neurological functions. However, there were no statistically significant differences between control and treated groups in terms of brain oedema at 48 h after ischaemic injury. 5. The findings of the present study may support the idea of a potential benefit of thiazolidinediones in the management of ischaemic stroke.     

Isoflurane inhaled at the onset of reperfusion potentiates the cardioprotective effect of ischemic postconditioning through a NO-dependent mechanism

Postconditioning (PCD) is known to reduce infarct size (IS). Here, we investigated whether isoflurane, which is known to potentiate preconditioning, also potentiates PCD and whether NO is involved. Accordingly, open-chest rabbits underwent 30-minute coronary artery occlusion (CAO) followed by 3-hour coronary artery reperfusion (CAR). In control and postconditioned (4 cycles of 30s-CAR/30s-CAO after the 30-min CAO), rabbits were anesthetized with pentobarbital alone or in combination with isoflurane inhaled (i) throughout the experiment or (ii) only during CAR. With pentobarbital alone, PCD significantly reduced IS versus control (39 +/- 7% vs. 55 +/- 4% of the risk zone, respectively, P < 0.05). Isoflurane--0.5% throughout the experiment did not alter IS in both control and PCD groups. Isoflurane--2% throughout the experiment reduced IS in control (37 +/- 8%, P < 0.05 vs. pentobarbital alone) and enhanced the protective effect of PCD (IS = 21 +/- 3%, P < 0.05 vs. both control and PCD under pentobarbital alone). When isoflurane--2% was administered only during reperfusion, IS was not changed in control (53 +/- 3%) but combination with PCD reduced IS to 23 +/- 4% (P < 0.05 vs. both control and PCD under pentobarbital alone). L-arginine analog N-nitro-L-arginine methyl ester administered before reperfusion did not properly alter IS (53 +/- 6%) but abolished the effect of PCD alone (IS = 47 +/- 7%) or in combination with isoflurane--2% during reperfusion (55 +/- 3%). Thus, isoflurane potentiates PCD at reperfusion through a NO-dependent mechanism.     

Human leukocyte antigen associations in basal cell carcinoma

Basal cell carcinoma is the most common form of skin cancer and is one in which both host and environmental factors are thought to play a role in its pathogenesis. For an investigation of the role of human leukocyte antigen (HLA)-associated variations in genetic susceptibility, thirty-one patients with multiple basal cell carcinomas were typed for HLA-A, B, C, and DR antigens. Patients were compared with both local and appropriate ethnic group controls. No statistically significant association with HLA-A, B, or C antigens was noted in any group. However, a significant increase in HLA-DR1 was noted in non-Irish, non-Ashkenazi patients. A tendency toward a decrease in HLA-DR3 was also noted among patients of Irish or Ashkenazi Jewish descent. The role of HLA-associated genetic factors in this form of skin cancer needs further investigation.     

Status of lipid peroxidation and antioxidant enzymes in goats naturally infected with Babesia ovis

This study aimed to assess lipid peroxidation and antioxidant enzymes in goats naturally infected with Babesia ovis. Red blood cell count (RBC), hemoglobin (Hb) concentration, packed cell volume (PCV), malondialdehyde (MDA) concentration, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities and total antioxidant capacity (TAC) were determined in 15 goats naturally infected with B. ovis as well as same number of healthy goats. The parasitological diagnosis was confirmed using polymerase chain reaction (PCR) analysis by amplifying a partial 18S rRNA gene sequence of B. ovis. Percentage of parasitemia varied from 0.01 to 1%. The activities of erythrocyte GSH-Px, SOD, CAT and TAC were significantly lower (p<0.05) in the infected goats than in healthy ones. MDA concentration in erythrocytes of infected goats was significantly higher in infected goats than in healthy ones (p?0.05). Severity of parasitemia showed a positive correlation with the MDA and negative correlation with PCV, SOD, CAT, GSH-Px and TAC. Also, MDA was negatively correlated with PCV, SOD, CAT, GSH-Px and TAC. The results of this study suggested that oxidative damage to RBCs may contribute to the pathogenesis of anemia in caprine babesiosis.     

Eliminating frown lines with an endoscopic forehead lift procedure (corrugator muscle disinsertion)

Background  

In certain cases of endoscopic forehead lift without muscle resection, patients were incidentally noted to develop weakness or loss of their ability to frown during the postoperative period despite intact musculature. This finding suggested the possibility of decreasing frown strength using the disinsertion of the relevant muscles. This finding persuaded the authors to try to eliminate or decrease the sensory problems resulting from open or endoscopic frowning muscle resection by disinserting these muscles. We therefore sought to determine the efficacy of a brow/forehead lift that involved disinsertion rather than muscle resection.     

Co-administration of subeffective anxiolytic doses of diazepam and hydroxyzine in elevated zero-maze in mice

Objective

Benzodiazepines are from the most common drugs which are used for treatment of anxiety disorders. There are other drugs with antianxiety properties including antihistamines such as hydroxyzine, too. Body of evidence show that co-administration of two drugs which act through different mechanisms, makes the dose of each drug to be reduced, while preserving the desired effect with less adverse drug reactions. The aim of this study was to see whether co-administration of subeffective antianxiety doses of diazepam and hydroxyzine has any antianxiety effect in elevated zero-maze (EZM) in mice.

Methods

To find the highest subeffective dose of each drug, different doses of hydroxyzine from 1.5 to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male mice. Thirty minutes later, the animals were placed on EZM and various parameters of anxiety were recorded by a camera to assess later. After determination of subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and diazepam was done and the anxiety parameters were measured.

Results

In co-administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as subeffective antianxiety doses of either drug, there were not any significant differences in main anxiety parameters, i.e., time spent in open areas and open area entries compared to control group. Hence, no anxiolytic effect was seen.

Conclusion

It seems that subeffective doses of diazepam and hydroxyzine may not have any facilitating or synergistic effect on each other in antianxiety responses in mice.     

Screening of the adult population in Iran for coeliac disease: comparison of the tissue-transglutaminase antibody and anti-endomysial antibody tests

BACKGROUND AND AIMS: Population-based studies for the prevalence of coeliac disease (CD) in west-Asian countries are scarce. We aimed to determine the prevalence of gluten-sensitive enteropathy (GSE) in the general population of northern and southern Iran, and evaluate the sensitivity and specificity of the anti-endomysial antibody (EMA) immunofluorescent test and the enzyme-linked immunosorbent assay-based test for determination of the IgA anti-tissue transglutaminase antibody (tTG-Ab) using the human recombinant transglutaminase antigen for the detection of CD in screening the asymptomatic adult population. MATERIAL AND METHODS: Using a stratified random sampling method we enrolled a total of 2799 individuals (1438 from Sari and 1361 from Kerman). The mean age was 33.7 years (range 18-66), with 1398 men. IgA anti-tissue transglutaminase (tTG) and IgA anti-EMA were determined in the serum of all subjects. Those participants with a positive serology for any of the two tests underwent small intestinal biopsy, and were classified according to revised Marsh criteria histologically. A diagnosis of GSE was based on positive serology and a compatible histopathological finding. The maximum likelihood latent class model was used to estimate the sensitivity and specificity of the two tests. RESULTS: Twenty-nine cases showed positive IgA tTG-Ab (15 men and 14 women, mean age 35.4 years, range 18-59), whereas only five were simultaneously positive for EMA. Except for two subjects with normal small bowel histology (Marsh 0), all other subjects were found to have biopsy findings compatible with GSE: 18 Marsh I, five Marsh II, three Marsh IIIa and one Marsh IIIc lesions. he prevalence of GSE was 0.96% or 1:104. The sensitivity and specificity of the human-recombinant IgA tTG-Ab assay were 100 and 99%, respectively, whereas the results for IgA EMA were 19 and 100%, respectively. The IgA EMA was positive in cases with advanced mucosal lesions of the small bowel. The mean serum value of IgA tTG-Ab was higher in patients with severe enteropathy compared with those showing slight mucosal changes (P<0.05). CONCLUSION: The minimum prevalence of gluten sensitivity among the general population of northern and southern Iran is 1:104. The best screening test for the detection of GSE in the general population is IgA tTG-Ab.